Data monitoring committees and interim monitoring guidelines

Most large randomized clinical trials have a data monitoring committee that periodically examines efficacy and safety results. A typical data monitori ng committee meets every 6 months, but the interim monitoring guidelines fo r many trials specify formal analyses that are years apart. In this article we argue that study protocols should include monitoring guidelines with fo rmal looks at each data monitoring committee meeting. Such guidelines are s hown to reduce the average duration of a trial with negligible effect on po wer and estimation bias. Some of the common statistical monitoring guidelin es require extreme evidence to stop a trial early and do not distinguish be tween stopping a trial during active accrual and follow-up stages. We propo se practical solutions for these issues. (C) Elsevier Science Inc. 1999.