NIH policy requiring independent data and safety monitoring boards (DSMB) for all multicenter Phase III trials has existed since 1979; the most recent restatement was issued in 1998 (NIH Policy for Data and Safety Monitoring, NIH Guide Notice 98-084). Further NIH guidance for Phase I and II trials was provided in 2000 (Further NIH Guidance on Data A Data and Safety Monitoring for Phase I and Phase II Trials, NIH Guide Notice OD-00-038). In light of the related responsibility for monitoring assigned to local Institutional Review Boards (IRB) by federal regulation (45 CFR 46), NIH added a requirement in 1999 that local IRBs be notified of the outcome of all DSMB reviews, even when no major change has been recommended, to document that data and safety monitoring is occurring as expected (Guidance on Reporting Adverse Events to Institutional Review Boards for NIH-Supported Multicenter Clinical Trials, NIH Guide Notice 99-107). These NIH policies do not address implementation matters, leaving those to individual Institutes and Centers. As a result, the National Institute of Allergy and Infectious Diseases (NIAID) has issued its own policy on basic principles for DSMB operations. The Division of AIDS (DAIDS) monitors safety and efficacy of multicenter randomized clinical trials primarily through standing DSMBs.
