Current issues in clinical research and the development of new pharmaceuticals

As a normal part of the drug development process, U.S. pharmaceutical companies conduct many thousands of clinical trials each year. Only after a reasonable assurance of safety is made can the drug be given to patients who have the underlying medical condition that the drug is designed to treat. Patient welfare is assured by adhering to the Food and Drug Administration's interpretation of the "common rule" if the data will be used to support a licensing application. 21 CFR Part 50 sets forth the regulations along with the principles of informed consent and the use of institutional review boards (IRBs) that assure patients' rights are protected. Any potential conflict of interest on the part of a clinical investigator must be reported to the FDA. Pharmaceutical companies extensively monitor ongoing clinical trials for compliance with appropriate regulations. The recent revision of the Declaration of Helsinki governing placebo-controlled clinical trials may adversely impact drug development.     

Neurobiological research involving human subjects: Perspectives from the office for protection from research risks

Department of Health and Human Services (HHS) regulations at 45 CFR 46 require that all human subjects research supported by HHS be reviewed and approved by a local Institutional Review Board (IRB). Investigators may not involve human subjects in research without their informed consent, and additional safeguards are required when subjects are likely to be vulnerable to coercion or undue influence. Application of the regulations to neurobiological research is discussed.     

International research: Ethical imperialism or ethical pluralism? 1

Conflicts have arisen in international research when countries in which research is being carried out lack the ethical rules or mechanisms for review employed in the United States and Europe. It is objected that a requirement to adhere to regulations promulgated by the US government constitutes “ethical imperialism.”; But if researchers in some countries need not be bound by ethical standards widely accepted in the conduct of research, it could open the door to an ethical relativism allowing virtually any standard a country desires to accept. One example is the variations in informed consent, especially in countries that accord lesser importance to the individual than do the US and Europe. A recent controversy centered on a series of placebo‐controlled, HIV/AIDS trials sponsored by the United States and conducted in several developing countries. These trials could not ethically be carried out in the United States because a proven effective treatment exists. Attempts to avoid similar controversies in forthcoming HIV/AIDS vaccine trials have been initiated by the joint United Nations AIDS program, with a process of regional consultations in the countries where the research will be conducted.     

Testing drugs in pediatric populations: The FDA mandate

On November 27, 1998 the Food and Drug Administration (FDA) issued a new rule requiring that drugs and biological products be tested in pediatric populations. Since voluntary testing in pediatric populations had not resulted in a significant increase in pediatric labeling of drugs, stronger measures were needed to ensure that infants and children would receive the benefits of properly tested drugs and biologies. The mandate for pediatric testing raises a core ethical question: How should the need for validated treatments that benefit children as a group be weighed against the obligation to protect individual child subjects of research? The preamble to the new rule claims that adherence to Department of Health and Human Services (DHHS) and American Academy of Pediatrics (AAP) guidelines will provide adequate protection to individual subjects. Yet the special protections provided to children in these guidelines are not required by the new FDA rule, and have never been obligatory for research that is regulated by the FDA. While the new rule does not necessitate or encourage violation of these standards, the rule does not pay adequate attention to them nor clarify what role they should play in IRB review of protocols under FDA regulation.     

Physician duties in the conduct of human subject research

In this article, I examine a skeptical argument against the possibility of ethically justifying risky human subject research (rHSR). That argument asserts that such research is unethical because it holds the possibility of wronging subjects who are harmed and whose consent to participate was less than fully voluntary. I conclude that the skeptical argument is not in the end sufficient to undermine the ethical foundation of rHSR because it fails to take account of the special positive duty researchers owe their clients and future patients. Although the skeptical argument is defeated, it exacts certain novel concessions from the pro‐research position. Of particular importance are the admissions (a) that researchers presumptively owe a fiduciary duty to research subjects, (b) that because the most important risks of rHSR are unknown and unquantifiable that duty must be explicitly waived by all subjects before they participate in any protocol, and (c) that such waivers must be made by individuals who satisfy objective criteria of competence for giving fully voluntary consent. The implementation of procedures responsive to these concerns might have a dampening effect on the conduct of research. However, the article concludes with a consideration of the likely benefits to researchers and society of a more cautious ethical regime.     

The protection of unrepresented patients in emergency care research

In emergency care research, it may be the case that neither informed consent nor surrogate consent is possible. In order to nonetheless allow for such research, codes and regulations of research ethics have increasingly incorporated provisions regarding this specific situation. The protection that those provisions offer need to be better understood. This article addresses in what ways they protect individuals, and especially the extent to which the suggested protection compensates for the loss of surrogate consent. The Declaration of Helsinki, the Additional Protocol to the Convention on Human Rights and Biomedicine, and the EU Clinical Trials Regulation serve as the main illustrations.     

Person-oriented research ethics: integrating relational and everyday ethics in research

Research ethics is often understood by researchers primarily through the regulatory framework reflected in the research ethics review process. This regulatory understanding does not encompass the range of ethical considerations in research, notably those associated with the relational and everyday aspects of human subject research. In order to support researchers in their effort to adopt a broader lens, this article presents a “person-oriented research ethics” approach. Five practical guideposts of person-oriented research ethics are identified, as follows: (1) respect for holistic personhood; (2) acknowledgement of lived world; (3) individualization; (4) focus on researcher-participant relationships; and (5) empowerment in decision-making. These guideposts are defined and illustrated with respect to different aspects of the research process (e.g., research design, recruitment, data collection). The person-oriented research ethics approach provides a toolkit to individual researchers, research groups, and research institutions in both biomedical and social science research wishing to expand their commitment to ethics in research.     

Disclosing Conflicts of Interest to Research Subjects: An Ethical and Legal Analysis

In this article, I examine the ethical and legal issues related to disclosure of conflicts of interest to research subjects, and discuss some empirical studies related to the topic. I argue that researchers have an ethical obligation to disclose conflicts of interest to research subjects, provided that they take steps to help subjects understand information about conflicts of interest and how to interpret it. Researchers also may have a legal duty to disclose conflicts of interests to subjects, depending on the facts of the case and the court's interpretation of the law. To reinforce and clarify the legal obligation to disclose conflicts of interest, the federal regulations should be amended to include disclosure of conflicts of interest as one of the informed consent requirements. Institutional review boards play a key role in helping researchers to disclose conflicts of interests to subjects in an appropriate manner. Institutional review boards should approve the disclosure language in informed consent documents, and they should require researchers to disclose financial interests to research subjects, if they have any, as a condition of approval.     

The Expanding Purview: Institutional Review Boards and the Review of Human Subjects Research

The implications of the institutional review board (IRB) system's growing purview are examined. Among the issues discussed are whether IRBs are censoring research and whether the IRB review process fundamentally alters the research that is being conducted. The intersection between IRB review and free speech is also explored. In general, it is argued that the review system for human subjects research (HSR) should be modified in order to limit the scope of IRB review.     

Guinea Pigs on the payroll: The ethics of paying research subjects

Regulatory bodies and scholars have traditionally conceptualized biomedical research on healthy subjects in the same way as research on patients. Guidelines and regulations have portrayed payment to a healthy subject as a potential constraint, or “undue influence,”; on the subject's free consent. In this essay we suggest an alternative way of conceptualizing research on healthy subjects, which sees the basic issue not as one of undue influence but as one of justice. Healthy subjects generally enroll in research protocols not for humanitarian reasons but for the money they will receive. Many of these protocols are conducted by profit‐driven corporations. Yet current guidelines and regulations prohibit subjects from negotiating for fair payment for the risks, discomforts and inconveniences they undergo, and IRBs are not staffed adequately to monitor the subject's safety. We propose to remedy the situation by regulating payment to healthy subjects as a labor relation.     

中国银行业直面世界金融业新发展的探索

金融机构的并购重组和商业银行的混业经营是经济发展的内在规律所决定的 ,是国际金融业发展的必然趋势。加入WTO后 ,中国银行业尤其是四大国有商业银行需要在正确判断世界金融业未来发展趋势的基础上 ,制定相应的发展战略 ,加快银行实践结构创新 ,对国有商业银行进行流程再造 ,以提升竞争力和抗风险能力。     

哲学观与哲学研究的重大问题(英文)

近年来,中国哲学界开展了当前马克思主义哲学研究的重大问题的讨论。人们对重大问题的不同看法,表现了对哲学性质和功能的理解等哲学观的差异,特别是对马克思哲学革命实质的理解的差异。本文认为,马克思的哲学革命终结了理论形而上学,但保留了传统哲学关于人的自由和全面发展的理想,保留了传统哲学超越的形而上学维度。只有进入和保持在哲学思维方式的水平上,才能有哲学意义和性质的重大问题研究,哲学思维方式仍是哲学研究的根本问题。     

环渤海区域经济发展战略初探

欧美日等发达国家和地区,经济圈约占其GDP(国内生产总值)的70%左右,而我国仅占30%左右。经济圈在我国方兴未艾,珠三角和长三角经济圈已显示出勃勃生机。环渤海经济圈至今未形成统一的发展格局,区域经济一体化和市场化水平低,经济差距有扩大的趋势。要振兴环渤海经济圈,发挥与其地位相称的作用,就应该在市场化和区域经济一体化的基础上,重点发挥首都经济圈、山东半岛城市群和辽中南地区三大支点的作用,推进渤海南北两翼,形成点轴发展格局,并根据区域优势,确定合理发展模式,带动整个区域的良性发展。     

社会主义社会发展动力系统

研究社会发展动力要抓住社会发展的主要矛盾,坚持普遍性与特殊性、层次性与系统性的结合.我国社会的发展动力是由多层次动力子系统构成的有机系统,各动力子系统又由动力因子、动力载体和动力激发机制三要素构成.不同动力子系统处于不同层次;不同动力要素系统发挥不同作用.加快社会发展,关键要从体制上建立精当的动力激发机制.     

北京市基层管理体制的历史变迁

城市基层管理体制是指基层政府组织城市居民的形式以及对之进行管理的方式方法 ,它既反映了国家与社会关系之间的互动 ,也反映了城市居民在社会发展中的地位和作用。本文从宏观上对北京市基层管理体制的历史变迁进行了梳理 ,认为北京市的基层管理体制在民国之前完成了从坊里制到保甲制的演变 ,民国之后 ,则逐步摆脱了“控制”的惯性 ,开始沿着“治理”思想的轨道前进。近年来由“街居—单位制”向“街道—社区制”的转型反映了北京市以人为本治理现代化大都市的新理念 ,具有非常重要的现实意义。     

Competence and consent to research: A critique of the recommendations of the national bioethics advisory commission*

Concern about the participation of incompetent subjects in psychiatric research has grown in the last several years. In response, the National Bioethics Advisory Commission (NBAC) recommended in its recent report that all investigations involving persons with mental disorders that may be associated with cognitive impairment that may pose greater than minimal risk to subjects utilize independent assessors to verify the capacities of subjects prior to entry into the study. This recommendation poses several problems for the conduct of research and the protection of research subjects. First, it fails to target that group of subjects most likely to be at risk for incapacity. Second, it focuses on too broad a range of research projects, many of which pose little risk to participants. The substantial costs of this approach are therefore not likely to be outweighed by concomitant benefits. In place of the NBAC recommendation, the author proposes a more flexible system of capacity assessment, designed to balance the costs with a greater likelihood of achieving meaningful protection for research subjects with mental disorders.     

Scaffolding and the zone of proximal development: A problematic relationship

For nearly four decades, a variety of social science disciplines have assumed that the zone of proximal development (ZPD) and the metaphor of scaffolding reflect more or less the same process. However, we will argue that any similarity is at best partial and at worst superficial. Equating the processes adds nothing to Vygotsky's general theory and in fact may weaken and dilute the robustness of the theory. To make the non‐equivalence case, the paper first presents an overview of Vygotsky's approach to psychology that includes an expansive discussion of the ZPD not only as the activity in which instruction leads development, but also as the key to his approach to experimental research. This is followed by a critical review of the relevant statements that have appeared in the literature on the nature of scaffolding, its presumed link to the ZPD and that brings to the fore the inadequacies of the metaphor itself that disqualify it as an equivalent process. While the ZPD can be understood to include the kind of interaction that is described in the scaffolding literature, it is a much broader and far more robust process than scaffolding, as is made apparent when the two processes are compared, which is the focus of the concluding section of the article. In the comparison we summarize the analyses presented, especially with regard to the implications and relevance of the metaphors underlying each concept.     

西部大开发的主体定位

正确的主体定位是西部大开发成功的前提。从现实条件、历史实证和国际比较的多重角度分析,西部大开发正确的主体定位应该是:开发主体是企业而不是政府、资本主体是民本经济而不是官本经济、服务主体是公务员服务企业家而不是企业家从属于公务员、规模主体是中小企业而不是大型企业、产业主体应该是自主选择而不是人为调整、战略主体应该是以人为本而不是以资源为本。     

经济全球化与中国政治发展战略目标

经济全球化条件下的中国政治发展战略目标,是指在经济全球化的时代背景下,中国政治发展使中国政治本身呈现何种状态,发展到什么样的水平和境界。这样的战略目标既要适应人类社会政治发展的历史潮流,体现政治发展的本质特征,又要从中国的实际出发。在经济全球化条件下,中国政治发展的战略目标是:政治民主化、政治法治化、政治稳定化和政治意识的核心价值体系的建构。