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流模式是由参与试验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推迟多中心研究的开始，并推迟患者获得潜在有益治疗的机会。尽管联邦法规允许替代审查模式以减少地方IRBs的重复工作，但这些替代方案的使用，包括使用 多中心试验的单一IRB记录(即中心IRB)是罕见的。为了反对对多中心试验审查监管框架的重大修订，并可能更直接地过渡到FDA、NIH和其他赞助商强制或强烈建议对多中心临床试验进行IRB审查的系统，迫切需要确定服从国内机构、政策制定者和其他关键利益攸关方的操作程序和指导原则。这项建议的主要目标是在多中心研究环境中为中心IRBs的原则和实践确定优先事项，并为参与IRB对多中心临床试验广告进行中央审查的机构和研究人员提出循证共识指导，为建议使用中央IRB进行多中心试验的赞助商提供指导。该项目的具体目标是：1)描述IRB对美国多中心研究的中央审查情况；2)领导利益相关者焦点小组，确定多中心研究环境中中央IRB的形成和实施的优先事项，以及对中央IRB吸收的伦理和监管障碍的感知；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央IRB的结构和职责的优先顺序；以及4)制定和发布关于多中心研究环境中中央IRB原则和实践的共识声明。该项目将包括对已出版和灰色文献的系统审查，各机构与选择进行IRB中央审查的IRBs之间现有协议的条款，以及国内IRBs现有的标准操作程序。系统审查的证据将纳入一系列有50个关键利益攸关方的有组织的重点小组，以便进一步发展中央和地方机构的责任，并使最重要的议题趋于一致。重点小组的调查结果将被纳入修改后的3轮德尔福共识调查，届时将邀请1,000多名利益攸关方确定中央机构预算的原则和做法的优先顺序。这是一个 综合的、以证据为基础的方法，目标是建立通用的术语、实践和程序，使参与开发或支持IRB审查多中心研究的更精简方法的美国利益相关者能够接受。这种严格的、最先进的方法的结果是共识指导，这将形成一个可持续和可复制的框架，用于IRB对多中心临床试验的中央审查。

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.