McNay Laura A, Tavel Jorge A, Oseekey Karen, McDermott Cathy M, Mollerup David, Bebchuk Judith D
National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1N223, Bethesda, MD 20892, USA.
Control Clin Trials. 2002 Feb;23(1):59-66. doi: 10.1016/s0197-2456(01)00183-0.
While accepted as serving an important function to safeguard human subjects, the process of obtaining regulatory approvals to conduct clinical trials is generally regarded as cumbersome and time-consuming. For large multinational trials, U.S. federally sponsored human subject research abroad involves specific U.S. regulatory requirements, in addition to those of the host country, that act as further hurdles. These requirements may include obtaining an Assurance of Protection for Human Subjects from the Office of Human Research Protection of the U.S. Department of Health and Human Services, maintaining specific Ethics Committee/Institutional Review Board (EC/IRB) composition, and incorporating mandated elements in informed consents, all of which may differ from local policies and guidelines. Specific examples of issues that led to delays in regulatory approvals for sites participating in the multinational clinical trial entitled Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) are presented here. While the goal of these requirements is to protect the rights and welfare of human subjects, they may create substantial delays and engender resentment over the notion of lack of respect for individual country sovereignty. Substudies within ESPRIT have been undertaken to obtain feedback from EC/IRB chairpersons, site personnel responsible for processing the required assurances, ESPRIT investigators, and study participants regarding aspects of current U.S. regulatory requirements related to human subject protection and ethical issues in multinational research. The purpose of these substudies is to compare the attitudes and experiences across countries regarding important ethical issues associated with conducting ESPRIT. One objective of the substudies is to gather additional insight to the impact of U.S. regulatory processes. Another is to help to inform the debate about how to best maximize the rights and welfare of clinical trial participants without delaying the initiation of research, while respecting the importance of national sensitivities.
虽然人们公认获得监管批准以开展临床试验的过程对保护人类受试者起着重要作用，但该过程通常被认为既繁琐又耗时。对于大型跨国试验而言，除了东道国的监管要求外，美国联邦政府资助的海外人体研究还涉及美国的特定监管要求，这些要求构成了更多障碍。这些要求可能包括从美国卫生与公众服务部人类研究保护办公室获得人类受试者保护保证、维持特定的伦理委员会/机构审查委员会（EC/IRB）组成，以及在知情同意书中纳入法定要素，所有这些都可能与当地政策和指南不同。本文介绍了导致参与名为“皮下白介素-2在随机国际试验中的评估”（ESPRIT）的跨国临床试验的各研究地点监管批准延迟的具体问题实例。虽然这些要求的目的是保护人类受试者的权利和福利，但它们可能会造成严重延误，并引发对缺乏对个别国家主权尊重这一观念的不满。ESPRIT内部已开展子研究，以获取来自EC/IRB主席、负责处理所需保证的研究地点人员、ESPRIT研究人员以及研究参与者关于当前美国与跨国研究中人类受试者保护及伦理问题相关监管要求的反馈。这些子研究的目的是比较各国在与开展ESPRIT相关的重要伦理问题上的态度和经验。子研究的一个目标是进一步深入了解美国监管程序的影响。另一个目标是帮助为关于如何在不延迟研究启动的情况下最大程度保障临床试验参与者的权利和福利，同时尊重各国敏感性重要性的辩论提供信息。
