With the collaboration of IRB leaders across its eight founding institutions, PEDSnet has made significant progress in developing regulatory policies and tools to facilitate research across the network.  All PEDSnet institutions endorse the PEDSnet Single Institutional Review Board (IRB) Policy which aims to establish a single IRB framework for multi-institutional research studies. The Single IRB framework provides a vehicle for investigators proposing multicenter studies to request "ceded review," that is, to request that the IRBs on a multicenter study rely on the review of one IRB, and for the IRBs at the participating institutions to elect to do so on a protocol-by-protocol basis.

From the launch the network, PEDSnet adapted and executed a Master Reliance Agreement among all its members, which set forth the respective authorities, roles, and responsibilities of each party when a ceded review arrangement is determined to be acceptable. With the NIH issuance of a final policy on the use of a Single IRB in January of 2018, PEDSnet along with other PCORnet collaborative network entities moved sites toward SMART IRB participation. The SMART IRB is an NIH Clinical and Translational Science Awards (CTSA) Program funded initiative which is designed to serve as a guide to meet the mandates of NIH funded multi-site trials. Currently, all PEDSnet members are participants in the SMART IRB Agreement.