Issues in clinical trial design: stopping a trial early and the large and simple trial.

Abstract

During the conduct of a clinical trial, a primary function of the Data Safety and Monitoring Committee is to select the trial conduct and the accumulating data to determine whether the trial should continue or be discontinued earlier than planned. Reasons for early discontinuation of a trial include: evidence of benefit, evidence of harm, and evidence of futility. More than 1 of these elements will often be present. These principles will be illustrated with examples from National Institute of Child Health and Human Development-Maternal-Fetal Medicine Units clinical trials. The "large and simple clinical trial" is a study design rarely undertaken in the United States but commonly used elsewhere. The principles of this type of trial will be introduced and contrasted with those of the "conventional clinical trial."