An ISO meets regularly with the principal investigator and study team to review the progress of the trial. In these meetings, the ISO discusses:  1) a review of any adverse safety events; 2) protocol deviations and exclusions; 3) enrollment and follow-up of participants; 3) missing data and data quality controls; 4) any new medical advances that may require changes in the study protocol. The timing of the meetings depends on the risk to the participants as well as the degree of oversight needed for a particular trial. If a clinical trial has regulatory lapses, excessive adverse events linked to the trial intervention, or fails to recruit adequate numbers of participants, the ISO may recommend that the clinical trial protocol be modified or the trial terminated. Occasionally, additional expertise beyond the ISO is needed to accomplish a comprehensive review. With additional personnel, this is considered a Safety Committee. Most frequently a biostatistician will be the additional reviewer. Other additions can include a content expert for nonclinical issues, a methodology consultant, or another clinician that has additional specific expertise.