Data from clinical studies generated by practice-based research networks (PBRNs) should be generalizable to the health care profession. For nationally representative data, a broad recruitment of practitioners may pose added risks to institutional review boards (IRBs). Infrastructure must assure data integrity while minimizing risk to assure that the clinical results are widely accepted across medical disciplines. The PEARL Network is an interdisciplinary dental/medical PBRN conducting a broad range of clinical studies. The infrastructure is designed to support the principles of good clinical practice (GCP) and create a data audit trail to ensure data integrity for generalizability. As the PBRN concept becomes of greater interest, membership may expand beyond the local community, and the issue of geography versus risk management becomes of concern to the IRB. The PEARL Network describes how it resolves many of the issues related to recruiting on a national basis while maintaining study compliance to ensure patient safety and minimize risk to the IRB.