Protocol Design - Establishing Criteria for Terminating or Re-Examining a Protocol

Investigators designing complex studies, such as those that utilize DSMCs, should incorporate into their protocols predetermined parameters or criteria that trigger a re-evaluation and potential revision of the protocol and that in some instances might even terminate the study. These criteria, which relate to the efficacy of a procedure or intervention, are assessed during interim data analysis when data are unblinded. This may occur approximately once per year or three to four times during a study. Every study that involves significant risk to the participants, such as oncology studies, should include a clear description of these criteria, define how often the data will be analyzed and compared to these criteria, and describe the decisions that are going to be made if these criteria are reached. A study plan that places human subjects at high risk and does not describe stopping guidelines that are appropriate in detail and content does not meet the standards of ethical research.