Consensus guidelines for central IRBs in the multicenter study setting

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.