Data monitoring committees and interim monitoring guidelines

Abstract

Most large randomized clinical trials have a data monitoring committee that periodically examines efficacy and safety results. A typical data monitoring committee meets every 6 months, but the interim monitoring guidelines for many trials specify formal analyses that are years apart. In this article we argue that study protocols should include monitoring guidelines with formal looks at each data monitoring committee meeting. Such guidelines are shown to reduce the average duration of a trial with negligible effect on power and estimation bias. Some of the common statistical monitoring guidelines require extreme evidence to stop a trial early and do not distinguish between stopping a trial during active accrual and follow-up stages. We propose practical solutions for these issues.