Consensus guidelines for central IRBs in the multicenter study setting

描述（由申请人提供）：多中心临床试验伦理审查的主要模式是由参与试验实施的每个机构的机构审查委员会（IRB）进行的分布式审查系统。对单一方案进行多次审查可能会延迟多中心研究的开始，并延迟患者获得潜在有益的治疗。尽管联邦法规允许采用替代性审查模式以减少地方IRB的重复工作，但使用这些替代性审查模式，包括使用 多中心试验的单个IRB记录（即，中心IRB），是一种罕见的情况。预计多中心临床试验审查监管框架将出现重大修订，并且可能会更快地过渡到一个系统，在该系统中，FDA、NIH和其他申办者强制要求或强烈建议采用更集中的方法对多中心临床试验进行IRB审查，因此迫切需要确定适用于国内机构、政策制定者、和其他主要利益相关者。本提案的主要目的是确定多中心研究环境中中心IRB原则和实践的优先顺序，并为参与中心IRB审查多中心临床试验的机构和研究者以及推荐使用中心IRB进行多中心试验的申办者提出循证共识指南。本项目的具体目的是：1）描述美国多中心研究的中心IRB审查状态; 2）组织利益相关者焦点小组，以确定中心IRB成立和开展的优先事项，以及在多中心研究环境中接受中心IRB的伦理和监管障碍; 3）对关键利益相关者进行共识调查，以确定多中心研究环境中中心IRB的结构和职责的优先顺序;以及4）制定并发布多中心研究环境中中心IRB原则和实践的共识声明。该项目将包括对已发表文献和灰色文献、选择进行中心IRB审查的机构和IRB之间的现有协议条款以及国内中心IRB的现有标准操作规程进行系统性审查。来自系统性综述的证据将被纳入一系列有50个关键利益相关者的结构化焦点小组，以进一步发展中央和地方IRB的职责，并实现最重要主题的趋同。焦点小组的调查结果将被纳入一项3轮修改后的德尔菲共识调查，其中将邀请1，000多名利益相关者对中央IRB的原则和做法进行优先排序。这是一 综合性、循证方法，旨在建立通用术语、实践和程序，这些术语、实践和程序适用于参与制定或支持更简化的多中心研究IRB审查方法的美国利益相关者。这种严格的最新技术水平方法的结果是共识指南，将形成可持续和可复制的多中心临床试验中心IRB审查框架的发展。

DESCRIPTION (provided by applicant): The prevailing model for ethical review of multicenter clinical trials is a distributed system of reviews conducted by the Institutional Review Board (IRB) of each institution engaged in the conduct of the trial. Conducting multiple reviews of a single protocol can delay the commencement of multicenter research and delay patient access to potentially beneficial treatments. Despite federal regulations that permit alternative review models to reduce duplication of effort by local IRBs, use of these alternatives, including use of a single IRB of record for a multicenter trial (i.e., central IRB), is a rare occurrence. In anticipaion of a major amendment to the regulatory framework for the review of multicenter trials and possibly more immediately, the transition to a system where a more centralized approach to IRB review of multicenter clinical trials is mandatory or strongly suggested by the FDA, NIH and other sponsors, there is an urgent need to identify operational procedures and guiding principles that are amenable to domestic institutions, policymakers, and other key stakeholders. The primary objective of this proposal is to establish priorities for the principles and practices of central IRBs in the multicenter study setting and propose evidence-based consensus guidance for institutions and investigators involved in central IRB review of a multicenter clinical trial ad for sponsors recommending use of central IRBs for multicenter trials. The specific aims of this project are to: 1) Describe the state of central IRB review of multicenter studies in the United States; 2) Conduct stakeholder focus groups to identify priorities for the formation and conduct of central IRBs and perceived ethical and regulatory barriers to uptake of central IRBs in the multicenter study setting; 3) Conduct a consensus survey of key stakeholders to prioritize the structure and responsibilities of a central IRB in the multicenter study setting; and 4) Develop and publish a consensus statement of principles and practices of central IRBs in the multicenter study setting. The project will include a systematic review of published and grey literature, the terms of existing agreements between institutions and IRBs choosing to undertake central IRB review, and the existing standard operating procedures of domestic central IRBs. The evidence from the systematic review will be integrated into a series of structured focus groups with 50 key stakeholders to allow further development of the responsibilities of central and local IRBs and achieve convergence of the topics of greatest importance. The findings of the focus groups will be incorporated into a 3 round modified Delphi consensus survey where over 1,000 stakeholders will be invited to prioritize the principles and practices of central IRBs. This is an integrative, evidence-based approach with the goal of establishing universal terminology, practices, and procedures that are amenable to US stakeholders engaged in developing or supporting a more streamlined approach to IRB review of multicenter research. The result of this rigorous, state of the art methodology is consensus guidance that will shape the development of a sustainable and replicable framework for central IRB review of multicenter clinical trials.