Statistical and Operational Issues Arising in an Interim Analysis When the Study Will Continue

Abstract

Guidelines for conducting interim analyses in clinical trials sponsored by the pharmaceutical industry have been recently published (1). Usually, the clinical trial will terminate or the design will change when the interim analysis shows outstanding efficacy results. There are situations, however, where the interim analysis shows outstanding efficacy results and yet the study continues, for example, when regulatory requirements in the United States and Europe differ concerning study duration. A case study is presented which describes the statistical and operational issues encountered while performing a two-year interim analysis of a three-year registration study when the study was to continue to the three-year timepoint with the same design regardless of the outcome of the interim analysis. The statistician plays a central role in developing and implementing the strategy to effectively resolve these issues.