AbstractData monitoring is a critical component of the conduct of clinical trials that provide the evidence of efficacy and safety of investigational drugs. These trials may be conducted either by a pharmaceutical sponsor or by the government, especially those large trials that assess the impact of therapies on serious morbidity and/or mortality. While not extensive, I will review a regulatory history of FDA's evolving concerns and positions on data monitoring. I will review the key aspects of data monitoring and interim analysis of clinical trials contained in the recently published International Conference on Harmonization's statistical guidance as well as some other issues being considered for a draft guidance on data monitoring. Finally, some suggestions for improving and enhancing tools and statistical methods for monitoring clinical trials for safety assessment will be offered. This latter area deserves more consideration by statisticians than it has received to date. Published in 2002 by John Wiley & Sons, Ltd.