Use of spending functions for occasional or continuous monitoring of data in clinical trials.

ABSTRACT

In many clinical trials, data are monitored periodically by an external data monitoring committee (DMC). Usually the frequency of these interim 'looks' at the data is prespecified. However, the progress of a clinical trial is unpredictable; often the schedule of looks must be modified. The Lan-DeMets procedure provides a spending function approach which does not require prespecification of the frequency or timing of interim looks. The procedure was developed based on the principle of a continuous Brownian motion process. In this paper we employ more elementary concepts to describe a procedure which is based upon the continuous monitoring of emerging data. The approach is flexible in that it applies to both continuous data monitoring and occasional interim monitoring. Examples are given from real clinical trials.